Presentation to Annual General Meeting
Released
Released
Announcement PDF
CEO’s presentation
Dr David Stamler
21 November 2025
Forward looking statements
2
This presentation may contain some statements that may be
considered “Forward-Looking Statements”, within the meaning
of the US Securities Laws. Thus, any forward-looking statement
relating to financial projections or other statements relating to
the Company’s plans, objectives, expectations or intentions
involve risks and uncertainties that may cause actual results to
differ materially. For a discussion of such risks and
uncertainties as they relate to us, please refer to our 2025 Form
20-F, filed with US Securities and Exchange Commission, in
particular Item 3, Section D, titled “Risk Factors.’’
Investment highlights
3
Positive Phase 2 data in
Multiple system atrophy
(MSA), an aggressive
Parkinsonian disorder
Large market potential
in neurodegenerative
diseases
Highly experienced
leadership team in
movement disorders
Oral administration
preferred over
competition
Robust efficacy on
functional endpoint in
double-blind study
Patient friendly
administration
Three FDA approvals in
neurology
ATH434 has Orphan Drug
designation for MSA treatment
Potential to treat Parkinson’s
disease and related disorders
Promising portfolio in neurodegenerative diseases
4
Program:
Drug
discovery
Indication: Discovery Pre-clinical Phase 1 Natural History
Positive topline data
Positive topline data
Phase 2 Phase 3 Collaboration
Multiple system atrophy
Open label study
Parkinson’s disease
Neurodegenerative
diseases
Friedreich’s ataxia
ATH434-201
ATH434-202
ATH434
ATH434
Multiple system atrophy
Natural history study
bioMUSE
Multiple system atrophy
Double blind study
Multiple System Atrophy (MSA):
Parkinsonian disorder with no approved treatment
0
Years: 3 6 9
7.5 years
median survival
after symptom onset
Over 50%
require wheelchair
in 5 years
Rapidly progressive
Highly debilitating
Up to 50,000
patients in U.S.
Disease characteristics:
• Motor: Parkinsonism, uncoordinated
movements, balance problems, falls
• Autonomic dysfunction: blood pressure
maintenance, bladder control, bowel function
• Atrophy and α-synuclein accumulation in
multiple brain regions
Premotor MSA Clinically probable MSA Death can occur
Clinically established MSA
Urinary dysfunction
REM sleep behavior disorder
Orthostatic hypotension
Multidomain
autonomic failure
Pyramidal signs
Parkinsonism
Cerebellar features
Recurrent falls
Indwelling catheter
Frontal executive dysfunction
Tracheostomy
Bronchopneumonia
Uroseptic fever
Unintelligible speech
Gastrostomy
5
Sources: Fanciulli, Wenning. NEJM 2015 | Wenning, et al. Mov Disorders 2022 | Coon, et al. Brain 2015 |
Multiple System Atrophy: National Institute of Neurological Disorders and Stroke (nih.gov)
Sudden death
ATH434: Small molecule drug candidate
6
Broad treatment
potential
Potential to treat many neurodegenerative
diseases (e.g., Parkinson’s, Frederich Ataxia)
Orphan & Fast Track
designations
US FDA Fast Track Designation and
Orphan drug designation in U.S. and EU
Blood-brain barrier
penetrant
Acts intracellularly to address underlying
pathology
Efficacy in animal
models of disease
Efficacy shown in animals with experimental
Parkinson’s disease and MSA
Oral administration Preferred by patients and doctors vs
infusions (IV, intrathecal) or injections
ATH434 binding
to labile iron
Targeting the pathology of MSA
8
Key players in MSA pathology
Two forms of iron required for cellular function:
• Energy production and activity of many enzymes
• Neurotransmitter synthesis (e.g., dopamine)
• Myelin synthesis
α-Synuclein protein:
• Present in all neurons
• Regulates neurotransmitter release
• Facilitates neuronal communication
Myelination
of axons
Fe2+
Fe3+
Fe2+ Reactive
Fe3+ Stable
Alpha-synuclein and iron balance vital for normal CNS function
Fe3+ Stable
Fe3+
Fe2+ Reactive
Fe2+
ATH434 mechanism of action: Iron chaperone
ATH434 redistributes excess labile (reactive) iron
to reduce neuronal injury
Sources: Adapted from Yanatori et al., BBA 2020 and Philpott et al., Frontiers Mol Bio. 2023 |
Pall, et al. Metallomics, 2024.
Efflux iron from
cell (ferroportin)
Increase iron
storage (ferritin)
Buffering Fe2+
in labile iron pool
PCBP: Poly(rC)-binding proteins
1
2
Fe3+
Fe2+
Endosome
Mitochondria
Ferritin
Ferroportin
DMT1
ZIP8
ZIP14
Transferrin
receptor
Labile iron
Fe2+
Fe2+
Fe2+
Fe2+
Fe2+
Fe2+
Fe2+
Fe2+
Fe2+
Fe2+
Fe2+
Fe2+
Fe2+
ATH434
ATH434
PCBP
PCBP
1
Fe2+
PCBP
2
Fe
3+
Tf
Fe
3+
PCBP
Enzyme
PCBP
ATH434
ROS
Fe2+
Fe2+
Fe2+
3
9
Redistribution
mechanisms:
3
Treatment approach: Address underlying pathology
10
Based on its
mechanism of
action, ATH434 is a
potential disease
modifying therapy
ATH434 redistributes
excess labile iron in the CNS
Reduces α-synuclein
aggregation and oxidative
injury
Preserves neurons and
oligodendrocyte support
cells
Stabilises or improves
patient function
ATH434 clinical development
program in MSA
Diligent approach to de-risk development program
12
• Observational study
in individuals with MSA
• Designed to de-risk clinical
development program
• Identify biomarkers to
improve accuracy of
patient selection
Phase 2
ATH434-201
ATH434-202
Randomized double-blind
placebo-controlled trial
Results: clinically meaningful efficacy on
MSA rating scale, measures of orthostatic
hypotension, disease severity
Natural History Study
Open label trial in advanced
MSA patients
Results: showed improved neurological
symptoms in more advanced patients and
favorable safety
bioMUSE
ATH434-201: Randomized, double-blind, placebo-controlled study
13
N=77
Study design: Endpoints:
Patient criteria:
• Clinical diagnosis of MSA
• Motor symptoms ≤4 years
• No severe impairment
• Elevated brain iron on MRI
• Elevated plasma NfL
Placebo twice daily
50 mg twice daily
Key clinical endpoint:
modified UMSARS Part 1
75 mg twice daily
ATH434
ATH434-201
MRI - Magnetic Resonance Imaging; UMSARS - Unified MSA Rating Scale (UMSARS) Scale– measures activities of daily living
CGI-S - Clinical Global Impression-Severity scale; OHSA - Orthostatic Hypotension Symptom Assessment
Additional secondary endpoints:
CGI-S, OHSA, Wearable Sensors,
Safety
ATH434
12 months treatment
Key biomarker endpoint:
brain iron content by MRI
Importance of the Unified MSA Rating Scale Part I (UMSARS I)
14
ATH434-201
Speech Walking
Swallowing Falling
Handwriting Orthostatic symptoms
Cutting food Urinary function
Dressing Bowel function
Hygiene Sexual function^
Validated rating scale to assess MSA disease severity
Rates functional impairment in domains affected in MSA
Rated from 0 to 48
higher scores worse
^ Modified version of UMSARS I excludes sexual function item
UMSARS Part I Items:
UMSARS is the
FDA endorsed
clinical endpoint
to support
approval for the
treatment of MSA
Clinically significant efficacy on modified UMSARS Part I
Change from baseline to week 52
15
ATH434-201
worsening
Modified
UMSARS
I
ATH434
50 mg
N=25
Placebo
N=22
ATH434
75 mg
N=24
- 3.8 (1.6) 48%
- 2.4 (1.7) 30%
Relative
treatment
effect
Difference
vs. placebo
LS mean (SE)
ChangeATH434 − Change Placebo
Change Placebo
Relative Treatment Effect
14
16
18
20
22
24
26
*
P=0.02
for 50 mg
0 13 26 39 52
P=0.16
for 75 mg
Clinical Analysis Population
ATH434
75 mg
N=24
- 2.8 (1.7) 35%
Effect of ATH434 75 mg strengthens when
correcting for important Baseline differences*
P-value 0.11
* Baseline ortho SBP change as
covariate given imbalance of
severe OH at baseline
Orthostatic Hypotension Symptom Assessment (OHSA)
Change from baseline to week 52
10
5
-5
0
Change
In
OHSA
(week
S2
BL)
• Assesses symptoms of low blood
pressure when going from sitting to
standing (e.g., dizziness / feeling faint /
lightheadedness)
• Patient reported outcome
p=0.08
worsening
mean (SE)
p=0.14
ATH434
50 mg
ATH434
75 mg
Placebo
16
Kaufmann, et al. Clin Auton Res 2012..
ATH434-201
Clinical Analysis Population
0
-50
-100
worsening
17
ATH434-201
Step count
worsening
0
-1000
-2000
-3000
Change
In
steps/day
p = 0.04
*
p = 0.10
Total time walking
Change
In
bouts/day
Total standing time
Pendant
Wearable movement sensor
ATH434-201
50 mg
ATH434-201
75 mg
Placebo
Change
In
minutes/day
0
-10
-20
-40
-30
p = 0.13
p = 0.15
worsening
Bouts of walking
0
-20
-40
-80
-60
Change
In
minutes/day
worsening
ATH434 preserved walking in outpatient setting
Change from baseline to week 52
Clinical Analysis Population
18
1 - Reporting one or more event
2 - None related to Study Drug
Placebo ATH434-201 ATH434-201
twice daily 50 mg 75 mg
Any Adverse Event (AE) 24 (92.3%) 21 (84.0%) 25 (96.2%)
N=25 N=26
N=26
ATH434-201
N (%) of subjects 1
• Similar rates of
AEs in ATH434
and placebo
participants
• No severe or
serious AEs
related to study
drug
• No hematologic
side effects
Severe AEs 2 8 (30.8%) 3 (12.0%) 6 (23.1%)
Serious AEs 2 10 (38.5%) 5 (20.0%) 7 (26.9%)
1 (3.8%) 3 (12.0%) 2 (7.7%)
2 (7.7%) 1 (4.0%) 5 (19.2%)
1 (3.8%) 6 (24.0%) 4 (15.4%)
8 (30.8%) 7 (28.0%) 8 (30.8%)
14 (53.8%) 10 (40.0%) 7 (26.9%)
Back pain
Fatigue
Covid-19
Fall
UTI
Adverse Events
ATH434-202: Open label study in advanced MSA
19
Key objective was
to assess efficacy
and safety of
ATH434 75 mg dose
for comparison to
75 mg dose in 201
double-blind study
Parameter
ATH434-202
75 mg BID
N=10
ATH434-201
75mg BID
N=24
Age (yr) 64.5 (7.5) 63.9 (6.7)
Duration of motor symptoms (yr) 3.9 (1.8) 2.3 (0.9)
Modified UMSARS I1 19.2 (5.3) 14.4 (4.4)
Motor score of Parkinson Plus Scale2 57.5 (20.4) 48.9 (16.8)
Plasma NfL (pg/mL) 42.1 (14.1) 32.3 (9.0)
OH Symptom Assessment 16.7 (14.8) 15.0 (12.2)
Severe Orthostatic Hypotension 40.0% 29.2%
Mean (SD)
1 MSA affected areas by MSA-atrophy index. Trujillo, P. et al Annals of Clin and Trans Neuro, 2025
Design Single arm, open-label
Population Advanced MSA (n=10)
Treatment ATH434 75 mg BID x 12 months
Brain MRI Biomarkers Iron, volume
Clinical Measures UMSARS I, clinical/patient global impressions of change
ATH434-202
Change over 12 Months
ATH434-202
75 mg BID
N=10
ATH434-201
75mg BID
N=24
Modified UMSARS I 3.5 (4.7) 5.6 (5.6)
Clinical global impression of change (% stable) 30% 21%
Patient global impression of change (% stable) 30% 26.4%
Brain volume1 -0.44 (0.14) -0.42 (0.29)
Mean (SD)
ATH434-202: Key data at 75 mg dose
Comparison to double blind study at 12 mo
20
• No serious AEs related to study drug
• AEs consistent with underlying disease
1 In MSA affected areas by MSA-atrophy index. Trujillo, P. et al. Annals of Clin and Trans Neuro, 2025
ATH434-202
The 75 mg dose
demonstrated
comparable efficacy
to that observed in
the double-blind
study
Approach to commercial assessment
Conducted by independent marketing research and forecasting group
21
• Conduct secondary market
research Assess unmet needs
and competitive landscape
• Develop target product
profile based on Phase 2 clinical
data
• Qualitative research
Conduct In-depth interviews
and Focus groups with
general neurologists,
movement disorder
neurologists and autonomic
specialists to identify decision-
making behavior and key
drivers and barriers to
adoption leveraging the target
product profile
• Develop physician screener
and discussion guide for
Quantitative Research
Exploratory Research
• Conduct ~30-minute online
survey among 100 neurologists
(~50% general, ~50% specialists)
to determine their awareness,
interest, market demand and
likelihood of product adoption
• Assess the Target Product
Profile to better understand its
viability, differentiation
opportunities and potential
barriers to adoption
• Rigorous methods used to
ensure data quality and
integrity
Quantitative Research
• Develop forecast assumptions
based on qualitative and
quantitative findings.
• Build a financial valuation of
ATH434 in treatment of MSA
Opportunity Analysis
and Forecast
Commercial opportunity in MSA
Key attributes of ATH434 drive significant value
22
USD $2.4 Billion
Potential worldwide annual peak sales for ATH434 in MSA
Severely debilitating illness
with no approved treatment
ripe for new entrants
Critical need for a tolerable,
disease modifying therapy
Importance of inhibiting
α‐synuclein aggregation to
address the underlying
pathology of disease
Over 70% of neurologists
were “extremely likely” or
“very likely’ to prescribe
ATH434 based on its profile
Slowing disease progression is
key driver of physician interest
Stabilizing orthostatic
hypotension^, one of the most
challenging symptoms in MSA,
strongly positions ATH434
^Orthostatic hypertension is the drop in blood pressure on standing; Global peak sales number in U.S. Dollars;
Independent market research survey conducted in 2025. Peak sales estimate based on U.S. prevalence of ~19,000
1 2 3 4
2025: Strengthening the Foundation for the Future
23
Phase 3 Trial Planning Ongoing with
FDA End-of-Phase 2 expected in mid-2026
ATH434-201 Positive Topline Data
ATH434-202 Positive Topline Data
Data presentations and publications:
Annals of Clinical and Translational Neurology:
Publication on MSA Atrophy Index
American Academy of Neurology (Platform Presentation)
American Autonomic Society (Oral Presentation)
American Neurological Association
International Congress of Parkinson's Disease &
Movement Disorders (Platform presentation)
International MSA Congress (Oral Presentation)
MSA Trust Symposium (Oral Presentation)
Key Data Readouts, FDA Interactions & Medical Community Engagement
FDA Fast Track Designation in MSA
5
Robust efficacy in
Phase 2 double-
blind trial on key
FDA endpoint
Accomplished
team with
multiple FDA
approvals in
neurology
Lead indication
MSA is an Orphan
Disease with no
approved
treatment
Open label trial
confirms
ATH434’s safety
and efficacy
profile
Cash Balance:
A $54.5M as of
30 September
ASX: ATH
NASDAQ: ATHE
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